Red blood cells at rest (stasis) forms aggregates, which are disaggregated gradually with increasing blood flow. The degree of aggregation and the aggregate structure reflect a delicate balance between chemical and hydrodynamic forces. In stasis, when flow forces are absent, the interaction between the cell membrane and plasma proteins will cause the red cells to aggregate into stacks called rouleaux, which further interact to form networks. Cell aggregation is a reversible process and the blood therefore follows dynamic changes according to flow conditions. The aggregability of red blood cells (hereinafter called RBC), which is a major determinant in blood circulation, strongly depends on the cells physical and chemical properties, and is very sensitive to changes in these properties. The size and number of red blood cell aggregates dominate the blood viscosity which plays a central role in blood flow in vessels of constant diameter. Thus the blood flow to tissues is largely affected by the aggregability of the RBC. The tendency of RBCs to form aggregates and thrombi under flow is a structural property of dynamic origin which is closely associated with the risk of diminished blood supply and the plugging of small blood vessels, pathologies which are important factors in stroke, shock, and damage caused to organs by various vascular diseases. The aggregation and disaggregation of RBC play a central role in blood flow, especially in microvessels and in states of lowered blood flow. Increased RBC aggregability occurs in many disease states (e.g. coronary heart diseases, diabetes, hyperviscosity syndrome, thrombosis, trauma and sickle cell anemia), and is considered to be a risk factor. Recent application of video microscopes enables a glimpse into this complicated type of flow. However, quantitative information about RBC organization under flow is still minimal, in spite of its great clinical significance.
Another important property of cells, particularly of blood cells, is their deformability, i.e. their ability to change shape and thus to pass through small blood vessels. Variations in the blood cells deformability contribute to various cardiovascular and microcirculatory disorders.
The present invention enables the visualization of RBC in a flow cell and analysis of the aggregability size and deformability under varying flow conditions. The depth of the flow cell is such that it enables a single layer of aggregates to pass through the cell, and provides a two dimensional array of the structures. The form of the cross section and the flow channel is important for generating flow gradients which are the origin of these disaggregating forces. This invention therefore is a novel and powerful tool for real-time monitoring of cell-to-cell interaction which is altered in pathological states and affected by drugs. This system enables study of the dynamic organization of cell suspensions; including flow related properties of such cells, such as cell deformability and shape, as well as the interaction between a cell or aggregate with the blood vessel wall, thus adding a new dimension to existing blood tests, and enriching the knowledge of blood rheology (the science of blood flow).
The creation of a flowing two dimensional aggregate layer requires a narrow gap. This imposes a practical problem of cleaning the flow cell and the tubing after each test. The problem becomes severe in the case of automatic testing in a commercial product that should withstand safety regulations.